Research Article Details
| Article ID: | A22170 |
| PMID: | 24769275 |
| Source: | Clin Biochem |
| Title: | Low normal thyroid function attenuates serum alanine aminotransferase elevations in the context of metabolic syndrome and insulin resistance in white people. |
| Abstract: | OBJECTIVES: Thyroid hormones play a key role in hepatic lipid metabolism. Although hypothyroidism is associated with increased prevalence of non-alcoholic fatty liver disease (NAFLD), the relationship of NAFLD with low normal thyroid function is unclear. We tested the association of serum alanine transferase (ALT), as a surrogate of NAFLD, with variations in thyroid function within the normal range. DESIGN AND METHODS: Thyroid stimulating hormone (TSH), free T4, ALT, insulin resistance (homeostasis model assessment (HOMA-IR)) and adiponectin were measured in 82 non-diabetic white subjects with TSH and free thyroxine (free T4) levels within the reference range. Nineteen participants were classified with metabolic syndrome (MetS). RESULTS: ALT was higher in MetS subjects (p<0.05), coinciding increased HOMA-IR (p<0.001). TSH and free T4 levels were not different in subjects with and without MetS. In all subjects combined, ALT was correlated positively with HOMA-IR and inversely with adiponectin (both p<0.001). Remarkably, ALT was correlated inversely with TSH in subjects with MetS (r=-0.642, p=0.003), but not in subjects without MetS (r=-0.132, p=0.30). Accordingly, in age- and sex-adjusted multivariable linear regression analysis the relationship of ALT with TSH was modified by the presence of MetS (interaction: β=-0.244, p=0.026), and likewise by HOMA-IR (interaction: β=-0.203, p=0.037). TSH also interacted with adiponectin on ALT (interaction: β=0.204, p=0.037). CONCLUSIONS: Low normal thyroid function may attenuate ALT elevations in the context of MetS and insulin resistance. It is conceivable that effect modification of low normal thyroid function on adiponectin-mediated pathways may be involved. |
| DOI: | 10.1016/j.clinbiochem.2014.04.016 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I04 | 1459 | Hypothyroidism | A thyroid gland disease which involves an underproduction of thyroid hormone. https://medlineplus.gov/hypothyroidism.html | disease of anatomical entity/ endocrine system disease/ thyroid gland disease | Details |
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D203 | Levothyroxine | Chemical drug | DB00451 | THRA agonist; THRB agonist | Anti-fibrosis | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |